This project investigates the interaction of factor VIII with other coagulation factors, particularly with factor IXa, activated protein C, calcium, ions, and phospholipid in the quaternary complex formed by these factors. The importance of proteolytic activation of factor VIII prior to its participation in the complex will be assessed, and the nonfunctional factor VIII molecule present in patients with hemophilia A will be studied to determine whether it can participate in the quaternary complex. The importance of platelets and platelet membranes vs. phospholipid will be assessed.